A critical feature of the immune system is the elimination of cells that are defective. Many B-cells are eliminated early in their development, however there is little information about the molecules that trigger this elimination. In mammals this process is difficult to study because B-cells develop in the bone marrow alongside other lineages of blood cells. The chicken has certain advantages as a model system of this process since B cells are formed in a single organ, the bursa of Fabricius, and many of them are eliminated during their development. We have described a novel molecule present on chicken B-lymphocytes that induces a rapid form of cell death and is capable of operating in species as divergent as mouse and chicken. This molecule is called chicken B6 (chB6, formerly called Bu-1). ChB6 is found almost exclusively on B-cells and, when bound by an anti-chB6 antibody, can trigger apoptosis in both avian and mammalian ceil lines. By virtue of its expression pattern and its ability to kill cells, chB6 must be considered a candidate molecule for initiating the cell death pathway in B-cells. The objectives of this project are to critically define, at the amino acid level, the specific regions within the chB6 molecule responsible for initiation of this death signal and to begin an earnest search for mammalian homologues of the chB6 molecule. This study is aimed at better defining the activity of chB6 and determining if similar molecules have been conserved in vertebrate evolution. By better understanding these issues we can begin to make hypotheses about defects that might lead to the failure to delete defective cells, potentially resulting in leukemia or autoimmune disease. [unreadable] [unreadable]